Exotic species have demonstrated their utility as models for the study of a wide range of hereditary and infectious diseases and physical traits. However, to fully interpret the results of these studies, it is necessary to understand their evolutionary history. This involves not only a more precise description of the phylogenetic relationships among species, but also an assessment of the uniqueness among wild populations and knowledge of historic patterns of gene flow. Our primary animal model has been the domestic cat and their exotic relatives and wild populations. As a crucial step in this process, we have developed the foremost collection of biological samples from captive and wild populations of cats, which has provided the theoretical and conceptual framework for our research. The recently-released whole genome sequence of the domestic cat has provided an important tool for our research and is greatly accelerating the pace of gene discovery and comparative genomic inference. The recently completed description of the evolution of the cat family will also facilitate more detailed study of selection and gene evolution among felid species and populations. Our comparative genomic studies are expanding to include the primate, camelid, and pangolin families. We will complete development of an RH map of the alpaca in 2006 which will facilitate the study of candidate genes for inherited diseases in camelids and related ungulate species, including several related to human disorders. Study of the pangolin, a group of species distributed in Africa and Asia and the closest relatives to carnivores, will provide good models for comparative genomic studies among these increasingly well-studied groups. A comprehensive phylogeny, linked with precise estimates of when and where different groups diverged will greatly enhance our ability to interpret human genetic variation in the context of human evolutionary history. Our research on primates, camelids, pangolins will be increasingly important given the inclusion of both the alpaca and the pangolin on the short list of species for low-coverage, whole-genome-sequencing. Our experience in comparative genomics and infectious disease is also being used to develop and test a model for the screening of animals being trafficed in wildlife trade for disease agents. The increasing contact of humans and domestic animals with wildlife has created conditions that have increased the likelihood of emerging diseases being spread that would have significant health and economic impact.